Minh Q. Nguyen, Nicholas J. P. Ryba

In mammals, odorants are detected by a large family of receptors that are each expressed in just a small subset of olfactory sensory neurons (OSNs). Here we describe a strain of transgenic mice engineered to express an octanal receptor in almost all OSNs. Remarkably, octanal triggered a striking and involuntary phenotype in these animals, with passive exposure regularly inducing seizures. Octanal exposure invariably resulted in widespread activation of OSNs but interestingly seizures only occurred in 30-40% of trials. We hypothesized that this reflects the need for the olfactory system to filter strong but slowly-changing backgrounds from salient signals. Therefore we used an olfactometer to control octanal delivery and demonstrated suppression of responses whenever this odorant is delivered slowly. By contrast, rapid exposure of the mice to octanal induced seizure in every trial. Our results expose new details of olfactory processing and provide a robust and non-invasive platform for studying epilepsy.